Transcatheter valve-in-ring implantation of a repositionable valve system for treatment of severe mitral regurgitation.

INTRODUCTION: Years after mitral valve surgery, progressive degeneration of reconstructed mitral valves or bioprostheses might lead to severe mitral valve regurgitation. Patients with significant comorbidity, or impaired left ventricular function are poor candidates for redo surgery at an acceptable risk at that later time point. METHODS AND RESULTS: This study reports the first-in-man transapical valve-in-ring implantations in the mitral position of the fully repositionable Lotus valve system approved for transcatheter aortic valve replacement in Europe. Transapical valve-in-ring implantations with this valve system were successfully performed in a 64-year-old female, and a 53-year-old male patient. Both patients were NHYA class IV, and carried an unacceptably high risk of cardiac surgery due to clinical condition and comorbidity. The first patient was successfully implanted a 25 mm valve, improved to NYHA class II, and was discharged 2 weeks after the procedure. The second patient required a short episode of cardiopulmonary resuscitation after valve implantation (27 mm), and was placed on veno-venous ECMO for 24 hr to improve oxygenation. He developed stroke on day 7, and deceased from fatal, toxic rhabdomyolysis 13 days after the procedure. CONCLUSION: Transapical valve-in-ring implantation of the repositionable Lotus valve system in the mitral position is a feasible and promising option that merits further evaluation. © 2015 Wiley Periodicals, Inc.

Surgical ablation of long-standing persistent atrial fibrillation: 1-year outcomes from the CArdioSurgEry Atrial Fibrillation (CASE-AF) registry.

OBJECTIVES: The CArdioSurgEry Atrial Fibrillation (CASE-AF) registry is a prospective, multicentre study for collecting and analysing real-world data of surgical atrial fibrillation (AF) treatment. This study aimed to evaluate outcomes of surgery for long-standing persistent AF at 1 year. METHODS: In total, 17 centres consecutively include all eligible patients with continuous AF lasting for ≥1 year. Exclusion criteria are missing informed consent or age <18 years. For patient-reported outcomes measures, the European Heart Rhythm Association score was used. No presence of AF (based on ECG findings including Holter ECG and/or implanted devices), no re-ablation, no further cardioversion and no rehospitalization due to AF after a 3-month blanking period defined no AF recurrence at 1 year. RESULTS: From January 2017 to January 2020, a total of 1115 patients were enrolled in CASE-AF. Of them, 202 patients (mean age 69.7 ± 7.8 years, 27.2% female) underwent surgical ablation of long-standing persistent AF (study cohort), mostly accompanied by left atrial appendage closure (n = 180 [89%], resection n = 75 [42%]) and predominantly performed as concomitant (n = 174 [86%]) and left atrial only procedure (n = 144 [71%]). Early mortality (30 days) was 2.0% and morbidity was low. At follow-up (median 14.4 months, interquartile range, 12.7-17.6 months, 100% complete), 106 patients (56%) had no AF recurrence and 93% of them were asymptomatic. AF recurrence was accompanied by AF-related rehospitalization (n = 12, P = 0.003), direct current shock cardioversion (n = 23, P < 0.001), AF ablation (n = 7, P = 0.003) and stroke (n = 3, P = 0.059). Multivariable analysis identified cryoablation, predominantly performed endocardially including additional left atrial (74%) and biatrial (42%) lesions, as a significant factor for freedom from AF recurrence (odds ratio 2.7, 95% confidence interval 1.07-6.79, P = 0.035). CONCLUSIONS: According to CASE-AF, surgical ablation of long-standing persistent AF is most effective when concomitantly performed using endocardial cryoablation. Ongoing follow-up allows further elucidation of efficacious treatment strategies.

Living Longer or Better-Patient's Choice in Cardiac Surgery Is Gender-Dependent-A Multicenter Study.

In view of the increasing age of cardiac surgery patients, questions arise about the expected postoperative quality of life and the hoped-for prolonged life expectancy. Little is known so far about how these, respectively, are weighted by the patients concerned. This study aims to obtain information on the patients' preferences. Between 2015 and 2017, data were analyzed from 1349 consecutive patients undergoing cardiac surgery at seven heart centers in Germany. Baseline data regarding the patient's situation as well as a questionnaire regarding quality of life versus lifespan were taken preoperatively. Patients were divided by age into four groups: below 60, 60-70, 70-80, and above 80 years. As a result, when asked to decide between quality of life and length of life, about 60% of the male patients opted for quality of life, independent of their age. On the other hand, female patients' preference for quality of life increased significantly with age, from 51% in the group below sixty to 76% in the group above eighty years. This finding suggests that female patients adapt their preferences with age, whereas male patients do not. This should impact further the treatment decisions of elderly patients in cardiac surgery within a shared decision-making process.

Topical Vancomycin Reduces the Incidence of Deep Sternal Wound Complications After Sternotomy.

BACKGROUND: Deep sternal wound infection remains a significant hazard for cardiosurgical patients undergoing median sternotomy. Although the prophylactic use of topical vancomycin to reduce the incidence of deep sternal wound complications (DSWC) has been repeatedly examined, the method remains controversial. METHODS: We report here on a continuous experience that encompassed a total of 1251 cardiosurgical patients who underwent various procedures via median sternotomy. Beginning in October 2015 and in response to a surge of DSWC (4.4%), 3 surgeons on our team began to apply 2.5 g vancomycin paste to the sternal edges just prior to closure, while the remaining 2 surgeons did not. An interim analysis comparing the 2 groups suggested that vancomycin was indeed effective, and from February 2016 on, all surgeons adopted the routine use of vancomycin in all patients. RESULTS: Retrospective analysis of 496 surgical patients from January to September 2015 had revealed a baseline incidence of DSWC of 4.4%. In the divided-use period between October 2015 and February 2016, DSWC was seen in 8.6% (8 of 93) of the no-vancomycin group. In the vancomycin group, the incidence fell to 0.8% (1 of 129). In March 2016, all surgeons began using vancomycin and the overall rate of DSWC for all surgeons and all patients subsequently declined to 1.1%. No adverse effects were observed. CONCLUSIONS: Topical vancomycin application is highly effective in the prevention of DSWC after median sternotomy.

External stenting and disease progression in saphenous vein grafts two years after coronary artery bypass grafting: A multicenter randomized trial.

OBJECTIVES: Little data exist regarding the potential of external stents to mitigate long-term disease progression in saphenous vein grafts. We investigated the effect of external stents on the progression of saphenous vein graft disease. METHODS: A total of 184 patients undergoing isolated coronary artery bypass grafting, using an internal thoracic artery graft and at least 2 additional saphenous vein grafts, were enrolled in 14 European centers. One saphenous vein graft was randomized to an external stent, and 1 nonstented saphenous vein graft served as the control. The primary end point was the saphenous vein graft Fitzgibbon patency scale assessed by angiography, and the secondary end point was saphenous vein graft intimal hyperplasia assessed by intravascular ultrasound in a prespecified subgroup at 2 years. RESULTS: Angiography was completed in 128 patients and intravascular ultrasound in the entire prespecified cohort (n = 51) at 2 years. Overall patency rates were similar between stented and nonstented saphenous vein grafts (78.3% vs 82.2%, P = .43). However, the Fitzgibbon patency scale was significantly improved in stented versus nonstented saphenous vein grafts, with Fitzgibbon patency scale I, II, and III rates of 66.7% versus 54.9%, 27.8% versus 34.3%, and 5.5% versus 10.8%, respectively (odds ratio, 2.02; P = .03). Fitzgibbon patency scale was inversely related to saphenous vein graft minimal lumen diameter, with Fitzgibbon patency scale I, II, and III saphenous vein grafts having an average minimal lumen diameter of 2.62 mm, 1.98 mm, and 1.32 mm, respectively (P < .05). Externally stented saphenous vein grafts also showed significant reductions in mean intimal hyperplasia area (22.5%; P < .001) and thickness (23.5%; P < .001). CONCLUSIONS: Two years after coronary artery bypass grafting, external stenting improves Fitzgibbon patency scales of saphenous vein grafts and significantly reduces intimal hyperplasia area and thickness. Whether this will eventually lead to improved long-term patency is still unknown.

Effects of the harvesting technique and external stenting on progression of vein graft disease 2 years after coronary artery bypass.

OBJECTIVES: In a post hoc analysis of the VEST III trial, we investigated the effect of the harvesting technique on saphenous vein graft (SVG) patency and disease progression after coronary artery bypass grafting. METHODS: Angiographic outcomes were assessed in 183 patients undergoing open (126 patients, 252 SVG) or endoscopic harvesting (57 patients, 114 SVG). Overall SVG patency was assessed by computed tomography angiography at 6 months and by coronary angiography at 2 years. Fitzgibbon patency (FP I, II and III) and intimal hyperplasia (IH) in a patient subset were assessed by coronary angiography and intravascular ultrasound, respectively, at 2 years. RESULTS: Baseline characteristics were similar between patients who underwent open and those who underwent endoscopic harvesting. Open compared with endoscopic harvesting was associated with higher overall SVG patency rates at 6 months (92.9% vs 80.4%, P = 0.04) and 2 years (90.8% vs 73.9%, P = 0.01), improved FP I, II and III rates (65.2% vs 49.2%; 25.3% vs 45.9%, and 9.5% vs 4.9%, respectively; odds ratio 2.81, P = 0.09) and reduced IH area (-31.8%; P = 0.04) and thickness (-28.9%; P = 0.04). External stenting was associated with improved FP I, II and III rates (odds ratio 2.84, P = 0.01), reduced IH area (-19.5%; P < 0.001) and thickness (-25.0%; P < 0.001) in the open-harvest group and reduced IH area (-12.7%; P = 0.01) and thickness (-9.5%; P = 0.21) in the endoscopic-harvest group. CONCLUSIONS: A post-hoc analysis of the VEST III trial showed that open harvesting is associated with improved overall SVG patency and reduced IH. External stenting reduces SVG disease progression, particularly with open harvesting.

Iatrogenic perforation of a pulmonary artery side branch-a case report.

BACKGROUND: The use of a pulmonary artery catheter (PAC) continues to be important for the diagnosis and therapeutic control of severe heart failure and in the diagnosis of pulmonary arterial hypertension. One of the most feared complications of this examination is perforation of a pulmonary artery with an estimated incidence of 0.031-0.05% and mortality rates of up to 70%. CASE SUMMARY: We report on an 80-year-old female patient who experienced a perforation of a pulmonary artery branch during the work-up of pulmonary arterial hypertension by PAC. Immediately after the perforation, haemodynamic shock developed rapidly, necessitating cardiopulmonary resuscitation. Occlusion of the pulmonary artery branch with a semicompliant balloon was applied immediately. After 40 min of occlusion, the bleeding persisted, and endovascular coil implantation was performed. Subsequently, the bleeding stopped, and the haemodynamics stabilized. After treatment, the patient was discharged home without any significant sequelae. DISCUSSION: Treatment options in pulmonary artery perforation are limited, especially if the patient is inoperable and if balloon occlusion fails. Based on our results, endovascular coil embolization can be considered a therapeutic option.

Argatroban and bivalirudin compared to unfractionated heparin in preventing thrombus formation on mechanical heart valves. Results of an in-vitro study.

Prevention of valve thrombosis in patients after prosthetic mechanical heart valve replacement and heparin-induced thrombocytopenia (HIT) is still an open issue. The aim of the present in-vitro study was to investigate the efficacy of argatroban and bivalirudin in comparison to unfractionated heparin (UFH) in preventing thrombus formation on mechanical heart valves. Blood (230 ml) from healthy young male volunteers was anticoagulated either by UFH, argatroban bolus, argatroban bolus plus continuous infusion, bivalirudin bolus, or bivalirudin bolus plus continuous infusion. Valve prostheses were placed in a newly developed in-vitro thrombosis tester and exposed to the anticoagulated blood samples. To quantify the thrombi, electron microscopy was performed, and each valve was weighed before and after the experiment. Mean thrombus weight in group 1 (UFH) was 117 + 93 mg, in group 2 (argatroban bolus) 722 + 428 mg, in group 3 (bivalirudin bolus) 758 + 323 mg, in group 4 (argatroban bolus plus continuous infusion) 162 + 98 mg, and in group 5 (bivalirudin bolus plus continuous infusion) 166 + 141 mg (p-value <0.001). Electron microscopy showed increased rates of thrombus formation in groups 2 and 3. Argatroban and bivalirudin were as effective as UFH in preventing thrombus formation on valve prostheses in our in-vitro investigation when they were administered continuously. We hypothesise that continuous infusion of argatroban or bivalirudin are optimal treatment options for patients with HIT after mechanical heart valve replacement for adapting oral to parenteral anticoagulation or vice versa.

Effects of aprotinin on gene expression and protein synthesis after ischemia and reperfusion in rats.

BACKGROUND: Reperfusion injury of ischemic myocardium has been attributed to neutrophil infiltration, inflammatory activation and cardiac necrosis/apoptosis. Serine protease inhibition with aprotinin is cardioprotective, but the mechanism is unknown. METHODS AND RESULTS: We studied aprotinin in a rat model of myocardial ischemia for 20 minutes and reperfusion for 20 minutes, 8 hours or 24 hours. Aprotinin (20,000 IU/kg) given 5 minutes before reperfusion significantly reduced leukocyte accumulation (P<0.01), myocardial injury (determined by CK depletion, P<0.01) and myocyte apoptosis (P<0.05) compared with vehicle treated rats. Differential gene expression analysis showed myocardial ischemia plus reperfusion increased expression of proinflammatory genes like P-selectin, E-selectin, intercellular adhesion molecule, tumor necrosis factor-alpha, tumor necrosis factor-alpha receptor, interleukin-6, monocyte chemoattractant protein-1, p53, and Fas (CD59). Aprotinin before reperfusion suppressed expression of these inflammatory genes. Finally, differential protein expression analysis demonstrated increased intercellular adhesion molecule-1, tumor necrosis factor-alpha, and p53 after myocardial ischemia plus reperfusion, and this effect was diminished by aprotinin. CONCLUSIONS: We demonstrated myocardial ischemia plus reperfusion induced leukocyte accumulation, inflammation, gene expression, protein expression and finally tissue injury and showed aprotinin limiting reperfusion injury through each of these stages, even after 24 hours of reperfusion. This effect seems partly attributable to suppression of proinflammatory genes and leukocyte accumulation. This work casts further light on the complex signaling of ischemia and reperfusion.

Age dependency of the cariporide-mediated cardio-protection after simulated ischemia in isolated human atrial heart muscles.

Experimental and clinical investigations suggest that blockade of Na(+)/H(+) exchange (NHE) with cariporide provides functional protection during ischemia and reperfusion in mature hearts. The benefit on aged human myocardium is unknown. Therefore, the impact of cardiac aging on cardio-protection by cariporide after prolonged ischemia was studied in isolated myocardium of adult (or=70 years) patients with coronary artery disease. Isolated atrial trabeculae were subjected to 30 min of simulated ischemia with and without cariporide, and early post-ischemic contractile recovery was determined. During the reoxygenation period, trabeculae of adults, but not those of old or very old patients, improved after treatment with cariporide. After 90 min of reoxygenation, cariporide-treated adult trabeculae developed 41+/-5% of their pre-ischemic force (non-treated control group, 27+/-5%; P<0.05), and old trabeculae recovered to 41+/-7% (control, 25+/-6%), whereas very old trabeculae recovered to only 26+/-2% (control, 28+/-6%). Trabeculae of all patients <70 years with CCS stage I-II angina pectoris recovered well (45+/-6%; control, 22+/-5%; P<0.01), which was in contrast to patients with CCS stage III (34+/-4%; control, 31+/-5%). Subsequent immunoblot analyses indicated no concomitant alterations in the myocardial NHE1 protein level depending on age. In very old myocardium, higher levels of active p38MAPK in atrial trabeculae after ischemia pointed at an increased cellular stress, which was even more pronounced after post-ischemic reperfusion. In summary, cariporide is protective against ischemia-reperfusion injury in mature human hearts but has no benefit on the post-ischemic functional recovery of the aging myocardium.

HeartMate II left ventricular assist device; early European experience.

OBJECTIVE: The novel axial flow left ventricular assist device HeartMate II was introduced into clinical practice in Europe as part of the pilot study and after CE approval in November 2005. In order to get an overview of the use and performance of the device in Europe a group of investigators was founded to compare the initial results. METHODS: In a retrospective analysis of the first 101 consecutive cases in Europe, data were collected with regard to postoperative outcome and severe adverse events and anticoagulation protocols. Results were stratified by intention to treat as a bridge to transplant or as chronic support therapy in heart failure (destination therapy). RESULTS: In 70% of patients, the HeartMate II was intended as a bridge to transplant therapy, in 30%, it was used as a destination therapy device. The perioperative mortality post implant was 20% in the bridge to transplant patients and 7% in the destination therapy arm. However, after 1 year a comparable survival was observed in both groups (69% destination therapy, 63% bridge to transplant). Main causes of death were multiple organ failure (n=12) and cerebrovascular accidents (n=5). All, but one cerebrovascular accident occurred in the first 9 days after surgery. Only one other death was reported thereafter and there was no mechanical failure of the device. CONCLUSIONS: Even in the early experience the HeartMate II was used as a chronic support device in a substantial number of patients in Europe. Although the total experience is still limited, the incidence of cerebrovascular accidents is very low and the survival beyond the perioperative period is excellent.

Neurological symptoms in type A aortic dissections.

BACKGROUND AND PURPOSE: Aortic dissection typically presents with severe chest or back pain. Neurological symptoms may occur because of occlusion of supplying vessels or general hypotension. Especially in pain-free dissections diagnosis can be difficult and delayed. The purpose of this study is to analyze the association between type A aortic dissection and neurological symptoms. METHODS: Clinical records of 102 consecutive patients with aortic dissection (63% male, median age 58 years) over 7.5 years were analyzed for medical history, preoperative clinical characteristics, treatment and outcome with main emphasis on neurological symptoms. RESULTS: Thirty patients showed initial neurological symptoms (29%). Only two-thirds of them reported chest pain, and most patients without initial neurological symptoms experienced pain (94%). Neurological symptoms were attributable to ischemic stroke (16%), spinal cord ischemia (1%), ischemic neuropathy (11%), and hypoxic encephalopathy (2%). Other frequent symptoms were syncopes (6%) and seizures (3%). In half of the patients, neurological symptoms were transient. Postoperatively, neurological symptoms were found in 48% of all patients encompassing ischemic stroke (14%), spinal cord ischemia (4%), ischemic neuropathy (3%), hypoxic encephalopathy (8%), nerve compression (7%), and postoperative delirium (15%). Overall mortality was 23% and did not significantly differ between patients with and without initial neurological symptoms or complications. CONCLUSIONS: Aortic dissections might be missed in patients with neurological symptoms but without pain. Neurological findings in elderly hypertensive patients with asymmetrical pulses or cardiac murmur suggest dissection. Especially in patients considered for thrombolytic therapy in acute stroke further diagnostics is essential. Neurological symptoms are not necessarily associated with increased mortality.

Depression of progenitor cell function by advanced glycation endproducts (AGEs): potential relevance for impaired angiogenesis in advanced age and diabetes.

Diabetes and ageing induce reduction and dysfunction of vascular progenitor cells. Advanced glycation endproducts (AGEs) accumulate in diabetes and ageing. We investigated the influence of AGEs on function of CD34 progenitor cells. CD34 cells were co-cultured with HUVECs in a three-dimensional spheroid assay. Sprout length growth and incorporation of CD34 cells into the sprouts were analyzed under 2, 20 or 200 microg/ml AGEs. AGE-receptor expression, MAP-kinase signal transduction and apoptosis were analyzed using PCR, Western blotting and flow cytometry. In the spheroid assay, AGEs concentration-dependently cause a reduction of sprout length growth by 6+/-6 to 32+/-6% and an attenuation of progenitor cells incorporation into the sprouting endothelium by up to 43+/-6%. This functional impairment is accompanied by activation of CD34 cell proliferation at lower concentrations (2 or 20 microg/ml) and by apoptosis activation under 200 microg/ml AGEs. The mRNA expression of the receptors for AGEs and the AGEs-induced activation of p38 and p44/42 MAP-kinases are demonstrable in CD34 cells. This AGEs-mediated impairment of progenitor cell function identifies a new pathophysiological mechanism of disturbed vascular adaptation in diabetes or ageing and suggests that lowering AGEs in recipients of progenitor cell therapy might be beneficial for the success of this therapy.

Prospective Multicenter Evaluation of the Direct Flow Medical Transcatheter Aortic Valve System: 12-Month Outcomes of the Evaluation of the Direct Flow Medical Percutaneous Aortic Valve 18F System for the Treatment of Patients With Severe Aortic Stenosis (DISCOVER) Study.

OBJECTIVES: The aim of this study was to assess the 1-year outcome after transcatheter aortic valve replacement (TAVR) of the Direct Flow Medical (DFM) valve in patients with severe symptomatic aortic stenosis who were contraindicated or high risk for surgery. BACKGROUND: The DFM transcatheter heart valve is a new-generation, nonmetallic aortic valve with a pressurized support structure and conformable double-ring annular sealing delivered through an 18-F sheath. The device allows repositioning, retrieval, and assessment of valve performance before permanent implantation. METHODS: A prospective multicenter European registry was set up to determine the safety and performance of the valve in 100 consecutive patients (10 centers). Echocardiographic and angiographic data were evaluated by an independent core laboratory, and adverse events were adjudicated by a clinical events committee using Valve Academic Research Consortium criteria. RESULTS: Patients were 83.1 ± 5.9 years of age and had a logistic EuroSCORE of 22.5 ± 11.3% and a Society of Thoracic Surgeons score of 9.7 ± 8.7%. Correct valve positioning was obtained in 99% of cases with a combined 30-day safety endpoint at 10%, including major stroke in 5.0%, major vascular complications in 2.0%, and death in 1%. At 12 months, 95% of patients were in New York Heart Association functional class I or II. Freedom from any death was 90%, and freedom from any death or major stroke was 85%. Echocardiography demonstrated none/trace to mild aortic regurgitation in 100% of patients and an unchanged mean aortic gradient of 12.2 ± 6.6 mm Hg and effective orifice area of 1.6 ± 0.4 cm(2). CONCLUSIONS: At 1 year, the DFM transcatheter heart valve had durable hemodynamics. This study demonstrates that the low rate of early complications and the low risk of significant aortic regurgitation translated into midterm clinical benefit.

An experimental approach to reversible 'endovascular aortic valve placement'.

BACKGROUND AND AIM OF THE STUDY: Beating heart aortic valve (re)placement without thoracotomy would be a desirable therapeutic strategy. In the present study, the feasibility of an endovascular aortic valve (re)placement was evaluated in an animal model. METHODS: A self-expandable stent-valve and two different non-obstructive delivery devices were designed. Initially, the stent-valve was temporarily placed via surgically dissected carotid and subclavian arteries. After retrieval of the stent-valve, an endovascular resection of the native aortic valve was performed, followed by definitive stent-valve implantation. All procedures were performed under echocardiographic guidance. RESULTS: Non-aortic vascular access was obtained in all animals. Via the carotid artery, the stent-valve was first placed into, and then retrieved from, the subcoronary position. Next, the native aortic valve was resected endovascularly, resulting in at least partial resection in all cases. The final step, definitive stent-valve implantation, was successful in all animals. The biological heart valve became functional after only a partial release of the stent. All animals remained hemodynamically stable after definitive implantation. Correct subcoronary position of the stent-valve was confirmed in a post-mortem examination. There was marked thrombus formation. CONCLUSION: The study results proved the feasibility of: (i) reversible stent-valve placement with a nonobstructive technique in the beating heart; and (ii) partial endovascular resection of the aortic valve, with both procedures achieved via non-aortic access.

Impact of surgical ventricular reconstruction on sphericity index in patients with ischaemic cardiomyopathy: follow-up from the STICH trial.

AIMS: We sought to evaluate associations between baseline sphericity index (SI) and clinical outcome, and changes in SI after coronary artery bypass graft (CABG) surgery with or without surgical ventricular reconstruction (SVR) in ischaemic cardiomyopathy patients enrolled in the SVR study (Hypothesis 2) of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. METHODS AND RESULTS: Among 1000 patients in the STICH SVR study, we evaluated 546 patients (255 randomized to CABG alone and 291 to CABG + SVR) whose baseline SI values were available. SI was not significantly different between treatment groups at baseline. After 4 months, SI had increased in the CABG + SVR group, but was unchanged in the CABG alone group (0.69 ± 0.10 to 0.77 ± 0.12 vs. 0.67 ± 0.07 to 0.66 ± 0.09, respectively; P < 0.001). SI did not significantly change from 4 months to 2 years in either group. Although LV end-systolic volume and EF improved significantly more in the CABG + SVR group compared with CABG alone, the severity of mitral regurgitation significantly improved only in the CABG alone group, and the estimated LV filling pressure (E/A ratio) increased only in the CABG + SVR group. Higher baseline SI was associated with worse survival after surgery (hazard ratio 1.21, 95% confidence interval 1.02 - 1.43; P = 0.026). Survival was not significantly different by treatment strategy. CONCLUSION: Although SVR was designed to improve LV geometry, SI worsened after SVR despite improved LVEF and smaller LV volume. Survival was significantly better in patients with lower SI regardless of treatment strategy.

Cardio-protective determinants are conserved in aged human myocardium after ischemic preconditioning.

Ischemic preconditioning (IPrec) improves post-ischemic dysfunctions of the myocardium along with activation of protein kinase C isozymes including PKCdelta. Moreover, expression of cardio-protective determinants can reduce ischemic damages. Because IPrec is limited in aged hearts, we assessed in an experimental model the impact of aging on PKCdelta and selected protective proteins in the preconditioned myocardium from adult (< or =55) and older (> or =70 years) humans. Adult myocardium showed PKCdelta up-regulation after IPrec along with improved post-ischemic contractility. Although there was no functional benefit, PKCdelta increased in older myocardium as well. Subsequent mRNA analyses demonstrated that IPrec stabilizes the mRNA expression of protective proteins (Hsp70, Bcl-2/-xL, IAPs) in both aging groups. Moreover, older hearts revealed increase in post-ischemic Hsp90beta. Our study indicates, that IPrec conserves the expression of cardio-protective determinants in aged hearts despite limited functional recovery.

Bronchoscopic surfactant administration preserves gas exchange and pulmonary compliance after single lung transplantation in dogs.

BACKGROUND: Surfactant abnormalities have been implicated in reperfusion injury and respiratory failure in lung transplantation. METHODS: We investigated the efficacy of bronchoscopic administration of a bovine natural lung surfactant extract (Alveofact) to improve gas exchange and lung mechanics after heterologous left lung transplantation in foxhounds (+4 degrees C ischemia for 24 hours, conservation with Euro-Collins solution). Animals received either no surfactant therapy (untreated controls, n = 6) or 50 mg/kg body weight (prior to explantation, only graft) and 200 mg/kg body weight Alveofact (immediately after reperfusion, both lungs, n = 6). After lung transplantation, separate but synchronized ventilation of each lung was performed in a volume-controlled, pressure-limited mode for 12 hours, with the animals prone. Small catheters were inserted into the pulmonary veins of both the graft and the recipient's native lung for separate blood gas analysis. In the control group, marked protein leakage, influx of neutrophils into the alveolar space, and pulmonary edema formation (extravascular lung water; wet/dry ratio) were encountered in the transplanted lung but only to a very minor extent in the recipient's native lung. RESULTS: Lung compliance values and arterial oxygenation progressively deteriorated in the transplanted but not in the native lungs. Pulmonary hemodynamics did not change significantly. Surfactant administration did not significantly influence the development of reperfusion edema, protein leakage, and neutrophil influx into the grafts. However, surfactant restored the surface activity and the gas exchange (PaO2/FIO2 of 201.2 +/- 20.2 mm Hg vs 119.8 +/- 21.7 mm Hg in controls; P <.05) in the transplanted lungs, and compliance was markedly improved in the surfactant-treated animals (18.8 +/- 1.8 mL/mbar vs 11.5 +/- 1.6 mL/mbar in the controls; P <.05). CONCLUSION: Bronchoscopic surfactant administration does not prevent leukocyte influx or vascular leakage but does protect against respiratory failure and improves lung mechanics in single lung transplantation in dogs.

Surfactant abnormalities after single lung transplantation in dogs: impact of bronchoscopic surfactant administration.

OBJECTIVE: Disturbances of the alveolar surfactant system have been implicated in the pathogenesis of reperfusion injury. The aim of this study was to evaluate the influence of exogenous surfactant administration on surfactant properties in a model of single lung transplantation. METHODS: We performed heterologous, left lung transplantation (+4 degrees C ischemia; 24 hours, Euro-Collins solution) in 6 foxhounds (untreated) and in 6 animals that received calf lung surfactant extract (Alveofact) prior to explantation (only donor lung; 50 mg/kg body weight) and immediately after onset of reperfusion (both lungs, 200 mg/kg body weight). Separate but synchronized ventilation of each lung was performed, in a volume-controlled, pressure-limited mode, with animals in prone position. Bronchoalveolar lavage fluids were collected in pretransplantation lungs (control), after 24 hours of ischemia prior to transplantation (0 hours) and 6 and 12 hours after reperfusion in both the grafts and the recipient native lungs. RESULTS: Ischemic storage per se did not provoke any changes of the surfactant system; however, severe alterations occurred within 6 hours of reperfusion, resulting in a severe loss of surface activity, including a decrease in the percentage of the large surfactant aggregate fraction, reduction of the surfactant apoproteins SP-B and SP-C, the dipalmitoyl molecular species of phosphatidylcholine and phosphatidylglycerol within the large surfactant aggregate fraction. These abnormalities were restricted to the graft, with virtually normal surfactant function and composition being found in the recipient native lung. Surfactant administration fully normalized the biochemical and largely improved the biophysical surfactant properties, alongside maintenance of lung gas exchange properties. CONCLUSIONS: Severe surfactant abnormalities occur exclusively in the graft when performing separate, synchronized ventilation of each lung to attenuate ventilator-induced lung injury. Bronchoscopic surfactant administration provides protection against these abnormalities and may be a therapeutic strategy in lung transplantation.

Ischemic preconditioning is not cardioprotective in senescent human myocardium.

BACKGROUND: Cellular and functional changes secondary to aging could impair myocardial tolerance to ischemia and affect the heart's response to ischemic preconditioning. METHODS: We investigated the impact of cardiac aging on preconditioning in right atrial trabeculae of adult patients (< or = 55 years) and senescent patients (> or = 70 years) with coronary artery disease. Specimens were subjected to 30 minutes of simulated ischemia (hypoxic substrate-free superfusion) with and without 5 minutes of ischemic pretreatment. Postischemic contractile recovery was measured and expressed as percentage of base line force values. RESULTS: During the reoxygenation period, trabeculae of adult patients but not those of senescent patients improved after ischemic preconditioning. After 40 minutes of reoxygenation, preconditioned adult trabeculae developed 57% +/- 5% of their preischemic force (nonpreconditioned control 44% +/- 5%, p < 0.01), senescent trabeculae recovered to 44% +/- 4% (control 45% +/- 3%). Especially myocardium from adult patients with Canadian Cardiovascular Society (CCS) stage III angina pectoris treated with ACE inhibitors recovered well (70% +/- 7%; control 50% +/- 8%, p < 0.01), contrasting with trabeculae from patients with CCS stage II angina (44% +/- 5%; control 40% +/- 10%). Ischemia-inducible Hsp70 (human heat shock protein) was additionally measured after reoxygenation. Total Hsp70 mRNA was elevated in preconditioned myocardium along with its contractile recovery (r = 0.33, p = 0.07). Because the control transcription, analyzing 18S rRNA and beta-actin, was reduced by ischemia but recovered in preconditioned trabeculae, relative Hsp70 mRNA was not altered. CONCLUSIONS: Our data indicate that ischemic preconditioning has no beneficial effect on the postischemic functional recovery of senescent human myocardium.